Apparatus and method for electromagnetic treatment of plant, animal, and human tissue, organs, cells, and molecules

ABSTRACT

An apparatus and method for electromagnetic treatment of plants, animals, and humans comprising: configuring at least one waveform according to a mathematical model having at least one waveform parameter, said at least one waveform to be coupled to a target pathway structure; choosing a value of said at least one waveform parameter so that said at least waveform is configured to be detectable in said target pathway structure above background activity in said target pathway structure; generating an electromagnetic signal from said configured at least one waveform; and coupling said electromagnetic signal to said target pathway structure using a coupling device.

This application claims the benefit of U.S. Provisional Application60/527,327 filed Dec. 5, 2003.

BACKGROUND OF THE INVENTION

1. Field of the Invention

This invention pertains generally to an apparatus and a method for invitro and in vivo therapeutic and prophylactic treatment of plant,animal, and human tissue, organs, cells and molecules. In particular, anembodiment according to the present invention pertains to use ofnon-thermal time-varying magnetic fields configured for optimal couplingto target pathway structures such as molecules, cells, tissue, andorgans, using power and amplitude comparison analysis to evaluate asignal to thermal noise ratio (“SNR”) in the target pathway structure.Another embodiment according to the present invention pertains toapplication of bursts of arbitrary waveform electromagnetic signals totarget pathway structures such as molecules, cells, tissues, and organsusing ultra lightweight portable coupling devices such as inductors andelectrodes, and driver circuitry that can be incorporated into apositioning device such as knee, elbow, lower back, shoulder, foot, andother anatomical wraps, as well as apparel such as garments, footware,and fashion accessories.

Yet another embodiment according to the present invention pertains toapplication of steady state periodic signals of arbitrary waveformelectromagnetic signals to target pathway structures such as molecules,cells, tissues, and organs. Examples of therapeutic and prophylacticapplications of the present invention are musculoskeletal pain relief,edema reduction, increased local blood flow, microvascular bloodperfusion, wound repair, bone repair, osteoporosis treatment andprevention, angiogenesis, neovascularization, enhanced immune response,tissue repair, enhanced transudation, and enhanced effectiveness ofpharmacological agents. An embodiment according to the present inventioncan also be used in conjunction with other therapeutic and prophylacticprocedures and modalities such as heat, cold, ultrasound, vacuumassisted wound closure, wound dressing, orthopedic fixation devices, andsurgical interventions.

2. Discussion of Related Art

It is now well established that application of weak non-thermalelectromagnetic fields (“EMF”) can result in physiologically meaningfulin vivo and in vitro bioeffects. Time-varying electromagnetic fields,comprising rectangular waveforms such as pulsing electromagnetic fields(“PEMF”), and sinusoidal waveforms such as pulsed radio frequency fields(“PRF”) ranging from several Hertz to an about 15 to an about 40 MHzrange, are clinically beneficial when used as an adjunctive therapy fora variety of musculoskeletal injuries and conditions.

Beginning in the 1960's, development of modern therapeutic andprophylactic devices was stimulated by clinical problems associated withnon-union and delayed union bone fractures. Early work showed that anelectrical pathway can be a means through which bone adaptively respondsto mechanical input. Early therapeutic devices used implanted andsemi-invasive electrodes delivering direct current (“DC”) to a fracturesite. Non-invasive technologies were subsequently developed usingelectrical and electromagnetic fields. These modalities were originallycreated to provide a non-invasive “no-touch” means of inducing anelectrical/mechanical waveform at a cell/tissue level. Clinicalapplications of these technologies in orthopaedics have led to approvedapplications by regulatory bodies worldwide for treatment of fracturessuch as non-unions and fresh fractures, as well as spine fusion.Presently several EMF devices constitute the standard armamentarium oforthopaedic clinical practice for treatment of difficult to healfractures. The success rate for these devices has been very high. Thedatabase for this indication is large enough to enable its recommendeduse as a safe, non-surgical, non-invasive alternative to a first bonegraft. Additional clinical indications for these technologies have beenreported in double blind studies for treatment of avascular necrosis,tendinitis, osteoarthritis, wound repair, blood circulation and painfrom arthritis as well as other musculoskeletal injuries.

Cellular studies have addressed effects of weak low frequencyelectromagnetic fields on both signal transduction pathways and growthfactor synthesis. It can be shown that EMF stimulates secretion ofgrowth factors after a short, trigger-like duration. Ion/ligand bindingprocesses at a, cell membrane are generally considered an initial EMFtarget pathway structure. The clinical relevance to treatments forexample of bone repair, is upregulation such as modulation, of growthfactor production as part of normal molecular regulation of bone repair.Cellular level studies have shown effects on calcium ion transport, cellproliferation, Insulin Growth Factor (“IGF-II”) release, and IGF-IIreceptor expression in osteoblasts. Effects on Insulin Growth Factor-I(“IGF-I”) and IGF-II have also been demonstrated in rat fracture callus.Stimulation of transforming growth factor beta (“TGF-β”) messenger RNA(“mRNA”) with PEMF in a bone induction model in a rat has been shown.Studies have also demonstrated upregulation of TGF-β mRNA by PEMF inhuman osteoblast-like cell line designated MG-63, wherein there wereincreases in TGF-β1, collagen, and osteocalcin synthesis. PEMFstimulated an increase in TGF-β1 in both hypertrophic and atrophic cellsfrom human non-union tissue. Further studies demonstrated an increase inboth TGF-β1 mRNA and protein in osteoblast cultures resulting from adirect effect of EMF on a calcium/calmodulin-dependent pathway.Cartilage cell studies have shown similar increases in TGF-β1 mRNA andprotein synthesis from EMF, demonstrating a therapeutic application tojoint repair. U.S. Pat. No. 4,315,503 (1982) to Ryaby and U.S. Pat. No.5,723,001 (1998) to Pilla typify the-research conducted in this field.

However, prior art in this field applies unnecessarily high amplitudeand power to a target pathway structure, requires unnecessarily longtreatment time, and is not portable.

Therefore, a need exists for an apparatus and a method that moreeffectively modulates biochemical processes that regulate tissue growthand repair, shortens treatment times, and incorporates miniaturizedcircuitry and light weight applicators thus allowing the apparatus to beportable and if desired disposable. A further need exists for anapparatus and method that more effectively modulates biochemicalprocesses that regulate tissue growth and repair, shortens treatmenttimes, and incorporates miniaturized circuitry and light weightapplicators that can be constructed to be implantable.

SUMMARY OF THE INVENTION

An apparatus and a method for delivering electromagnetic signals tohuman, animal and plant target pathway structures such as molecules,cells, tissue and organs for therapeutic and prophylactic purposes. Apreferred embodiment according to the present invention utilizes a PowerSignal to Noise Ratio (“Power SNR”) approach to configure bioeffectivewaveforms and incorporates miniaturized circuitry and lightweightflexible coils. This advantageously allows a device that utilizes aPower SNR approach, miniaturized circuitry, and lightweight flexiblecoils, to be completely portable and if desired to be constructed asdisposable and if further desired to be constructed as implantable.

Specifically, broad spectral density bursts of electromagneticwaveforms, configured to achieve maximum signal power within a bandpassof a biological target, are selectively applied to target pathwaystructures such as living organs, tissues, cells and molecules.Waveforms are selected using a unique amplitude/power comparison withthat of thermal noise in a target pathway structure. Signals comprisebursts of at least one of sinusoidal, rectangular, chaotic and randomwave shapes, have frequency content in a range of about 0.01 Hz to about100 MHz at about 1 to about 100,000 bursts per second, and have a burstrepetition rate from about 0.01 to about 1000 bursts/second. Peak signalamplitude at a target pathway structure such as tissue, lies in a rangeof about 1 μV/cm to about 100 mV/cm. Each signal burst envelope may be arandom function providing a means to accommodate differentelectromagnetic characteristics of healing tissue. A preferredembodiment according to the present comprises a 20 millisecond pulseburst comprising about 5 to about 20 microsecond symmetrical orasymmetrical pulses repeating at about 1 to about 100 kilohertz withinthe burst. The burst envelope is a modified 1/f function and is appliedat random repetition rates. A resulting waveform can be delivered viainductive or capacitive coupling.

It is an object of the present invention to configure a power spectrumof a waveform by mathematical simulation by using signal to noise ratio(“SNR”) analysis to configure an optimized, bioeffective waveform thencoupling the configured waveform using a generating device such as ultralightweight wire coils that are powered by a waveform configurationdevice such as miniaturized electronic circuitry.

It is another object of the present invention to evaluate Power SNR forany target pathway structure such as molecules, cells, tissues andorgans of plants, animals and humans using any input waveform, even ifthe electrical equivalents are non-linear as in a Hodgkin-Huxleymembrane model.

It is another object of the present invention to provide a method andapparatus for treating plants, animals and humans using electromagneticfields selected by optimizing a power spectrum of a waveform to beapplied to a chosen biochemical target pathway structure such as amolecule, cell, tissue and organ of a plant, animal, and human.

It is another object of the present invention to employ significantlylower peak amplitudes and shorter pulse duration. This can beaccomplished by matching via Power SNR, a frequency range in a signal tofrequency response and sensitivity of a target pathway structure such asa molecule, cell, tissue, and organ, of plants, animals and humans.

The above and yet other objects and advantages of the present inventionwill become apparent from the hereinafter set forth Brief Description ofthe Drawings, Detailed Description of the Invention, and Claims appendedherewith.

BRIEF DESCRIPTION OF THE DRAWINGS

Preferred embodiments of the present invention will be described belowin more detail, with reference to the accompanying drawings:

FIG. 1 is a flow diagram of a method for electromagnetic treatment ofplant, animal, and human target pathway structures such as tissue,organs, cells, and molecules according to an embodiment of the presentinvention;

FIG. 2 is a view of control circuitry and electrical coils applied to aknee joint according to a preferred embodiment of the present invention;

FIG. 3 is a block diagram of miniaturized circuitry according to apreferred embodiment of the present invention;

FIG. 4A is a line drawing of a wire coil such as an inductor accordingto a preferred embodiment of the present invention;

FIG. 4B is a line drawing of a flexible magnetic wire according to apreferred embodiment of the present invention;

FIG. 5 depicts a waveform delivered to a target pathway structure suchas a molecule, cell, tissue or organ according to a preferred embodimentof the present invention;

FIG. 6 is a view of a positioning device such as a wrist supportaccording to a preferred embodiment of the present invention;

FIG. 7 is a graph illustrating maximally increased myosinphosphorylation for a PMRF signal configured according to an embodimentof the present invention; and

FIG. 8 is a graph illustrating a power consumption comparison between a60 Hz signal and a PEMF signal configured according to an embodiment ofthe present invention.

DETAILED DESCRIPTION

Induced time-varying currents from PEMF or PRF devices flow in a targetpathway structure such as a molecule, cell, tissue, and organ, and it isthese currents that are a stimulus to which cells and tissues can reactin a physiologically meaningful manner. The electrical properties of atarget pathway structure affect levels and distributions of inducedcurrent. Molecules, cells, tissue, and organs are all in an inducedcurrent pathway such as cells in a gap junction contact. Ion or ligandinteractions at binding sites on macromolecules that may reside on amembrane surface are voltage dependent processes, that iselectrochemical, that can respond to an induced electromagnetic field(“E”). Induced current arrives at these sites via a surrounding ionicmedium. The presence of cells in a current pathway causes an inducedcurrent (“J”) to decay more rapidly with time (“J(t)”). This is due toan added electrical impedance of cells from membrane capacitance andtime constants of binding and other voltage sensitive membrane processessuch as membrane transport.

Equivalent electrical circuit models representing various membrane andcharged interface configurations have been derived. For example, inCalcium (“Ca²⁺”) binding, the change in concentration of bound Ca²⁺ at abinding site due to induced E may be described in a frequency domain byan impedance expression such as:${Z_{b}(\omega)} = {R_{ion} + \frac{1}{{\mathbb{i}\omega}\quad C_{ion}}}$which has the form of a series resistance-capacitance electricalequivalent circuit. Where ω is angular frequency defined as 2πf, where fis frequency, i=−1½, Z _(b)(ω) is the binding impedance, and R_(ion) andC_(ion) are equivalent binding resistance and capacitance of an ionbinding pathway. The value of the equivalent binding time constant,τ_(ion)=R_(ion)C_(ion), is related to a ion binding rate constant,k_(b), via τ_(ion)=R_(ion)C_(ion)=1/k_(b). Thus, the characteristic timeconstant of this pathway is determined by ion binding kinetics.

Induced E from a PEMF or PRF signal can cause current to flow into anion binding pathway and affect the number of Ca²⁺ ions bound per unittime. An electrical equivalent of this is a change in voltage across theequivalent binding capacitance C_(ion), which is a direct measure of thechange in electrical charge stored by C_(ion). Electrical charge isdirectly proportional to a surface concentration of Ca²⁺ ions in thebinding site, that is storage of charge is equivalent to storage of ionsor other charged species on cell surfaces and junctions. Electricalimpedance measurements, as well as direct kinetic analyses of bindingrate constants, provide values for time constants necessary forconfiguration of a PMF waveform to match a bandpass of target pathwaystructures. This allows for a required range of frequencies for anygiven induced E waveform for optimal coupling to target impedance, suchas bandpass.

Ion binding to regulatory molecules is a frequent EMF target, forexample Ca²⁺ binding to calmodulin (“CaM”). Use of this pathway is basedupon acceleration of wound repair, for example bone repair, thatinvolves modulation of growth factors released in various stages ofrepair. Growth factors such as platelet derived growth factor (“PDGF”),fibroblast growth factor (“FGF”), and epidermal growth factor (“EGF”)are all involved at an appropriate stage of healing. Angiogenesis isalso integral to wound repair and modulated by PMF. All of these factorsare Ca/CaM-dependent.

Utilizing a Ca/CaM pathway a waveform can be configured for whichinduced power is sufficiently above background thermal noise power.Under correct physiological conditions, this waveform can have aphysiologically significant bioeffect.

Application of a Power SNR model to Ca/CaM requires knowledge ofelectrical equivalents of Ca²⁺ binding kinetics at CaM. Within firstorder binding kinetics, changes in concentration of bound Ca²⁺ at CaMbinding sites over time may be characterized in a frequency domain by anequivalent binding time constant, τ_(ion)=R_(ion)C_(ion), where R_(ion)and C_(ion) are equivalent binding resistance and capacitance of the ionbinding pathway. τ_(ion) is related to a ion binding rate constant,k_(b), via τ_(ion)=R_(ion)C_(ion)=1/k_(b). Published values for k_(b)can then be employed in a cell array model to evaluate SNR by comparingvoltage induced by a PRF signal to thermal fluctuations in voltage at aCaM binding site. Employing numerical values for PMF response, such asV_(max)=6.5×10⁻⁷ sec⁻¹, [Ca²⁺]=2.5 μM, K_(D)=30 μM, [Ca²⁺CaM]=K_(D)([Ca²⁺]+[CaM]), yields k_(b)=665 sec⁻¹ (τ_(ion)=1.5 msec). Such a valuefor τ_(ion) can be employed in an electrical equivalent circuit for ionbinding while power SNR analysis can be performed for any waveformstructure.

According to an embodiment of the present invention a mathematical modelcan be configured to assimilate that thermal noise is present in allvoltage dependent processes and represents a minimum thresholdrequirement to establish adequate SNR. Power spectral density, S_(n)(ω),of thermal noise can be expressed as:S _(n)(ω)=4 kT Re[Z _(M)(x,ω)]where Z_(M)(x,ω) is electrical impedance of a target pathway structure,x is a dimension of a target pathway structure and Re denotes a realpart of impedance of a target pathway structure. Z_(M)(x,ω) can beexpressed as:${Z_{M}\left( {x,\omega} \right)} = {\left\lbrack \frac{R_{e} + R_{i} + R_{g}}{\gamma} \right\rbrack{\tanh\left( {\gamma\quad x} \right)}}$

This equation clearly shows that electrical impedance of the targetpathway structure, and contributions from extracellular fluid resistance(“R_(e)”), intracellular fluid resistance (“R_(i)”) and intermembraneresistance (“R_(g)”) which are electrically connected to a targetpathway structure, all contribute to noise filtering.

A typical approach to evaluation of SNR uses a single value of a rootmean square (RMS) noise voltage. This is calculated by taking a squareroot of an integration of S_(n)(ω)=4 kT Re[Z_(M)(x,ω)] over allfrequencies relevant to either complete membrane response, or tobandwidth of a target pathway structure. SNR can be expressed by aratio: ${SNR} = \frac{{V_{M}(\omega)}}{R\quad{MS}}$where |V_(M)(ω)| is maximum amplitude of voltage at each frequency asdelivered by a chosen waveform to the target pathway structure.

Referring to FIG. 1, wherein FIG. 1 is a flow diagram of a method fordelivering electromagnetic signals to target pathway structures such asmolecules, cells, tissue and organs of plants, animals, and humans fortherapeutic and prophylactic purposes according to an embodiment of thepresent invention. A mathematical model having at least one waveformparameter is applied to configure at least one waveform to be coupled toa target pathway structure such as a molecule, cell, tissue, and organ(Step 101). The configured waveform satisfies a SNR or Power SNR modelso that for a given and known target pathway structure it is possible tochoose at least one waveform parameter so that a waveform is detectablein the target pathway structure above its background activity (Step 102)such as baseline thermal fluctuations in voltage and electricalimpedance at a target pathway structure that depend upon a state of acell and tissue, that is whether the state is at least one of resting,growing, replacing, and responding to injury. A preferred embodiment ofa generated electromagnetic signal is comprised of a burst of arbitrarywaveforms having at least one waveform parameter that includes aplurality of frequency components ranging from about 0.01 Hz to about100 MHz wherein the plurality of frequency components satisfies a PowerSNR model (Step 102). A repetitive electromagnetic signal can begenerated for example inductively or capacitively, from said configuredat least one waveform (Step 103). The electromagnetic signal is coupledto a target pathway structure such as a molecule, cell, tissue, andorgan by output of a coupling device such as an electrode or aninductor, placed in close proximity to the target pathway structure(Step 104). The coupling enhances a stimulus to which cells and tissuesreact in a physiologically meaningful manner.

FIG. 2 illustrates a preferred embodiment of an apparatus according tothe present invention. A miniature control circuit 201 is coupled to anend of at least one connector 202 such as wire. The opposite end of theat least one connector is coupled to a generating device such as a pairof electrical coils 203. The miniature control circuit 201 isconstructed in a manner that applies a mathematical model that is usedto configure waveforms. The configured waveforms have to satisfy a SNRor Power SNR model so that for a given and known target pathwaystructure, it is possible to choose waveform parameters that satisfy SNRor Power SNR so that a waveform is detectable in the target pathwaystructure above its background activity. A preferred embodimentaccording to the present invention applies a mathematical model toinduce a time-varying magnetic field and a time-varying electric fieldin a target pathway structure such as a molecule, cell, tissue, andorgan, comprising about 10 to about 100 msec bursts of about 1 to about100 microsecond rectangular pulses repeating at about 0.1 to about 10pulses per second. Peak amplitude of the induced electric field isbetween about 1 uV/cm and about 100 mV/cm, varied according to amodified 1/f function where f=frequency. A Waveform configured using apreferred embodiment according to the present invention may be appliedto a target pathway structure such as a molecule, cell, tissue, andorgan for a preferred total exposure time of under 1 minute to 240minutes daily. However other exposure times can be used. Waveformsconfigured by the miniature control circuit 201 are directed to agenerating device 203 such as electrical coils via connector 202. Thegenerating device 203 delivers a pulsing magnetic field configuredaccording to a mathematical model, that can be used to provide treatmentto a target pathway structure such as knee joint 204. The miniaturecontrol circuit applies a pulsing magnetic field for a prescribed timeand can automatically repeat applying the pulsing magnetic field for asmany applications as are needed in a given time period, for example 10times a day. A preferred embodiment according to the present inventioncan be positioned to treat the knee joint 204 by a positioning device.The positioning device can be portable such as an anatomical support,and is further described below with reference to FIG. 6. Coupling apulsing magnetic field to a target pathway structure such as a molecule,cell, tissue, and organ, therapeutically and prophylactically reducesinflammation thereby reducing pain and promotes healing. When electricalcoils are used as the generating device 203, the electrical coils can bepowered with a time varying magnetic field that induces a time varyingelectric field in a target pathway structure according to Faraday's law.An electromagnetic signal generated by the generating device 203 canalso be applied using electrochemical coupling, wherein electrodes arein direct contact with skin or another outer electrically conductiveboundary of a target pathway structure. Yet in another embodimentaccording to the present invention, the electromagnetic signal generatedby the generating device 203 can also be applied using electrostaticcoupling wherein an air gap exists between a generating device 203 suchas an electrode and a target pathway structure such as a molecule, cell,tissue, and organ. An advantage of the preferred embodiment according tothe present invention is that its ultra lightweight coils andminiaturized circuitry allow for use with common physical therapytreatment modalities and at any body location for which pain relief andhealing is desired. An advantageous result of application of thepreferred embodiment according to the present invention is that a livingorganism's wellbeing can be maintained and enhanced.

FIG. 3 depicts a block diagram of a preferred embodiment according tothe present invention of a miniature control circuit 300. The miniaturecontrol circuit 300 produces waveforms that drive a generating devicesuch as wire coils described above in FIG. 2. The miniature controlcircuit can be activated by any activation means such as an on/offswitch. The miniature control circuit 300 has a power source such as alithium battery 301. A preferred embodiment of the power source has anoutput voltage of 3.3 V but other voltages can be used. In anotherembodiment according to the present invention the power source can be anexternal power source such as an electric current outlet such as anAC/DC outlet, coupled to the present invention for example by a plug andwire. A switching power supply. 302 controls voltage to amicro-controller 303. A preferred embodiment of the micro-controller 303uses an 8 bit 4 MHz micro-controller 303 but other bit MHz combinationmicro-controllers may be used. The switching power supply 302 alsodelivers current to storage capacitors 304. A preferred embodiment ofthe present invention uses storage capacitors having a 220 uF output butother outputs can be used. The storage capacitors 304 allow highfrequency pulses to be delivered to a coupling device such as inductors(Not Shown). The micro-controller 303 also controls a pulse shaper 305and a pulse phase timing control 306. The pulse shaper 305 and pulsephase timing control 306 determine pulse shape, burst width, burstenvelope shape, and burst repetition rate. An integral waveformgenerator, such as a sine wave or arbitrary number generator can also beincorporated to provide specific waveforms. A voltage level conversionsub-circuit 308 controls an induced field delivered to a target pathwaystructure. A switching Hexfet 308 allows pulses of randomized amplitudeto be delivered to output 309 that routes a waveform to at least onecoupling device such as an inductor. The micro-controller 303 can alsocontrol total exposure time of a single treatment of a target pathwaystructure such as a molecule, cell, tissue, and organ. The miniaturecontrol circuit 300 can be constructed to apply a pulsing magnetic fieldfor a prescribed time and to automatically repeat applying the pulsingmagnetic field for as many applications as are needed in a given timeperiod, for example 10 times a day. A preferred embodiment according tothe present invention uses treatments times of about 10 minutes to about30 minutes.

Referring to FIGS. 4A and 4B a preferred embodiment according to thepresent invention of a coupling device 400 such as an inductor is shown.The coupling device 400 can be an electric coil 401 wound withmultistrand flexible magnetic wire 402. The multistrand flexiblemagnetic wire 402 enables the electric coil 401 to conform to specificanatomical configurations such as a limb or joint of a human or animal.A preferred embodiment of the electric coil 401 comprises about 10 toabout 50 turns of about 0.01 mm to about 0.1 mm diameter multistrandmagnet wire wound on an initially circular form having an outer diameterbetween about 2.5 cm and about 50 cm but other numbers of turns and wirediameters can be used. A preferred embodiment of the electric coil 401can be encased with a non-toxic PVC mould 403 but other non-toxic mouldscan-also be used.

Referring to FIG. 5 an embodiment according to the present invention ofa waveform 500 is illustrated. A pulse 501 is repeated within a burst502 that has a finite duration 503. The duration 503 is such that a dutycycle which can be defined as a ratio of burst duration to signal periodis between about 1 to about 10⁻⁵. A preferred embodiment according tothe present invention utilizes pseudo rectangular 10 microsecond pulsesfor pulse 501 applied in a burst 502 for about 10 to about 50 msechaving a modified 1/f amplitude envelope 504 and with a finite duration503 corresponding to a burst period of between about 0.1 and about 10seconds.

FIG. 6 illustrates a preferred embodiment according to the presentinvention of a positioning device such as a wrist support. A positioningdevice 600 such as a wrist support 601 is worn on a human wrist 602. Thepositioning device can be constructed to be portable, can be constructedto be disposable, and can be constructed to be implantable. Thepositioning device can be used in combination with the present inventionin a plurality of ways, for example incorporating the present inventioninto the positioning device for example by stitching, affixing thepresent invention onto the positioning device for example by Velcro®,and holding the present invention in place by constructing thepositioning device to be elastic. In another embodiment according to thepresent invention, the present invention can be constructed as astand-alone device of any size with or without a positioning device, tobe used anywhere for example at home, at a clinic, at a treatmentcenter, and outdoors. The wrist support 601 can be made with anyanatomical and support material, such as neoprene. Coils 603 areintegrated into the wrist support 601 such that a signal configuredaccording to the present invention, for example the waveform depicted inFIG. 5, is applied from a dorsal portion that is the top of the wrist toa plantar portion that is the bottom of the wrist. Micro-circuitry 604is attached to the exterior of the wrist support 601 using a fasteningdevice such as Velcro® (Not Shown). The micro-circuitry is coupled toone end of at least one connecting device such as a flexible wire 605.The other end of the at least one connecting device is coupled to thecoils 603. Other embodiments according to the present invention of thepositioning device include knee, elbow, lower back, shoulder, otheranatomical wraps, and apparel such as garments, fashion accessories, andfootware.

EXAMPLE 1

The Power SNR approach for PMF signal configuration has been testedexperimentally on calcium dependent myosin phosphorylation in a standardenzyme assay. The cell-free reaction mixture was chosen forphosphorylation rate to be linear in time for several minutes, and forsub-saturation Ca²⁺ concentration. This opens the biological window forCa²⁺/CaM to be EMF-sensitive. This system is not responsive to PMF atlevels utilized in this study if Ca²⁺ is at saturation levels withrespect to CaM, and reaction is not slowed to a minute time range.Experiments were performed using myosin light chain (“MLC”) and myosinlight chain kinase (“MLCR”) isolated from turkey gizzard. A reactionmixture consisted of a basic solution containing 40 mM Hepes buffer, pH7.0; 0.5 mM magnesium acetate; 1 mg/ml bovine serum albumin, 0.1% (w/v)Tween 80; and 1 mM EGTA12. Free Ca²⁺ was varied in the 1-7 μM range.Once Ca²⁺ buffering was established, freshly prepared 70 nM CaM, 160 nMMLC and 2 nM MLCK were added to the basic solution to form a finalreaction mixture. The low MLC/MLCK ratio allowed linear time behavior inthe minute time range. This provided reproducible enzyme activities andminimized pipetting time errors.

The reaction mixture was freshly prepared daily for each series ofexperiments and was aliquoted in 100 μL portions into 1.5 ml Eppendorftubes. All Eppendorf tubes containing reaction mixture were kept at 0°C. then transferred to a specially designed water bath maintained at37±0.1° C. by constant perfusion of water prewarmed by passage through aFisher Scientific model 900 heat exchanger. Temperature was monitoredwith a thermistor probe such as a Cole-Parmer model 8110-20, immersed inone Eppendorf tube during all experiments. Reaction was initiated with2.5 μM 32 P ATP, and was stopped with Laemmli Sample Buffer solutioncontaining 30 μM EDTA. A minimum of five blank samples were counted ineach experiment. Blanks comprised a total assay mixture minus one of theactive components Ca²⁺, CaM, MLC or MLCK. Experiments for which blankcounts were higher than 300 cpm were rejected. Phosphorylation wasallowed to proceed for 5 min and was evaluated by counting 32 Pincorporated in MLC using a TM Analytic model 5303 Mark V liquidscintillation counter.

The signal comprised repetitive bursts of a high frequency waveform.Amplitude was maintained constant at 0.2 G and repetition rate was 1burst/sec for all exposures. Burst duration varied from 65 μsec to 1000μsec based upon projections of Power SNR analysis which showed thatoptimal Power SNR would be achieved as burst duration approached 500μsec. The results are shown in FIG. 7 wherein burst width 701 in μsec isplotted on the x-axis and Myosin Phosphorylation 702 as treated/sham isplotted on the y-axis. It can be seen that the PMF effect on Ca²⁺binding to CaM approaches its maximum at approximately 500 μsec, just asillustrated by the Power SNR model.

These results confirm that a PMF signal, configured according to anembodiment of the present invention, would maximally increase myosinphosphorylation for burst durations sufficient to achieve optimal PowerSNR for a given magnetic field amplitude.

EXAMPLE 2

According to an embodiment of the present invention use of a Power SNRmodel was further verified in an in vivo wound repair model. A rat woundmodel has been well characterized both biomechanically andbiochemically, and was used in this study. Healthy, young adult maleSprague Dawley rats weighing more than 300 grams were utilized.

The animals were anesthetized with an intraperitoneal dose of Ketamine75 mg/kg and Medetomidine 0.5 mg/kg. After adequate anesthesia had beenachieved, the dorsum was shaved, prepped with a dilute betadine/alcoholsolution, and draped using sterile technique. Using a #10 scalpel, an8-cm linear incision was performed through the skin down to the fasciaon the dorsum of each rat. The wound edges were bluntly dissected tobreak any remaining dermal fibers, leaving an open wound approximately 4cm in diameter. Hemostasis was obtained with applied pressure to avoidany damage to the skin edges. The skin edges were then closed with a 4-0Ethilon running suture. Post-operatively, the animals receivedBuprenorphine 0.1-0.5 mg/kg, intraperitoneal. They were placed inindividual cages and received food and water ad libitum.

PMF exposure comprised two pulsed radio frequency waveforms. The firstwas a standard clinical PRF signal comprising a 65 μsec burst of 27.12MHz sinusoidal waves at 1 Gauss amplitude and repeating at 600bursts/sec. The second was a PRF signal reconfigured according to anembodiment of the present invention. For this signal burst duration wasincreased to 2000 μsec and the amplitude and repetition rate werereduced to 0.2 G and 5 bursts/sec respectively. PRF was applied for 30minutes twice daily.

Tensile strength was performed immediately after wound excision. Two 1cm width strips of skin were transected perpendicular to the scar fromeach sample and used to measure the tensile strength in kg/mm². Thestrips were excised from the same area in each rat to assure consistencyof measurement. The strips were then mounted on a tensiometer. Thestrips were loaded at 10 mm/min and the maximum force generated beforethe wound pulled apart was recorded. The final tensile strength forcomparison was determined by taking the average of the maximum load inkilograms per mm² of the two strips from the same wound.

The results showed average tensile strength for the 65 μsec 1 Gauss PRFsignal was 19.3±4.3 kg/mm² for the exposed group versus 13.0±3.5 kg/mm²for the control group (p<0.01), which is a 48% increase. In contrast,the average tensile strength for the 2000 μsec 0.2 Gauss PRF signal,configured according to an embodiment of the present invention using aPower SNR model was 21.2±5.6 kg/mm² for the treated group versus13.7±4.1 kg/mm² (p<0.01) for the control group, which is a 54% increase.The results for the two signals were not significantly different fromeach other.

These results demonstrate that an embodiment of the present inventionallowed a new PRF signal to be configured that could be produced withsignificantly lower power. The PRF signal configured according to anembodiment of the present invention, accelerated wound repair in the ratmodel in a low power manner versus that for a clinical PRF signal whichaccelerated wound repair but required more than two orders of magnitudemore power to produce.

EXAMPLE 3

In this example Jurkat cells react to PMF stimulation of a T-cellreceptor with cell cycle arrest and thus behave like normalT-lymphocytes stimulated by antigens at the T-cell receptor such asanti-CD3. For example in bone healing, results have shown both 60 Hz andPEMF fields decrease DNA synthesis of Jurkat cells, as is expected sincePMF interacts with the T-cell receptor in the absence of a costimulatorysignal. This is consistent with an anti-inflammatory response, as hasbeen observed in clinical applications of PMF stimuli. The PEMF signalis more effective. A dosimetry analysis performed according to anembodiment of the present invention demonstrates why both signals areeffective and why PEMF signals have a greater effect than 60 Hz signalson Jurkat cells in the most EMF-sensitive growth stage.

Comparison of dosimetry from the two signals employed involvesevaluation of the ratio of the Power spectrum of the thermal noisevoltage that is Power SNR, to that of the induced voltage at theEMF-sensitive target pathway structure. The target pathway structureused is ion binding at receptor sites on Jurkat cells suspended in 2 mmof culture medium. The average peak electric field at the binding sitefrom a PEMF signal comprising 5 msec burst of 200 μsec pulses repeatingat 15/sec, was 1 mV/cm, while for a 60 Hz signal it was 50 μV/cm.

FIG. 8 is a graph of results wherein Induced Field Frequency 801 in Hzis plotted on the x-axis and Power SNR 802 is plotted on the y-axis.FIG. 8 illustrates that both signals have sufficient Power spectrum thatis Power SNR≈1, to be detected within a frequency range of bindingkinetics. However, maximum Power SNR for the PEMF signal issignificantly higher than that for the 60 Hz signal. This is because aPEMF signal has many frequency components falling within the bandpass ofthe binding pathway. The single frequency component of a 60 Hz signallies at the mid-point of the bandpass of the target pathway. The PowerSNR calculation that was used in this example is dependant upon τ_(ion)which is obtained from the rate constant for ion binding. Had thiscalculation been performed a priori it would have concluded that bothsignals satisfied basic detectability requirements and could modulate anEMF-sensitive ion binding pathway at the start of a regulatory cascadefor DNA synthesis in these cells. The previous examples illustrated thatutilizing the rate constant for Ca/CaM binding could lead to successfulprojections for bioeffective EMF signals in a variety of systems.

Having described embodiments for an apparatus and a method fordelivering electromagnetic treatment to human, animal and plantmolecules, cells, tissue and organs, it is noted that modifications andvariations can be made by persons skilled in the art in light of theabove teachings. It is therefore to be understood that changes may bemade in the particular embodiments of the invention disclosed which arewithin the scope and spirit of the invention as defined by the appendedclaims.

1) A method for electromagnetic treatment of plants, animals, and humanscomprising the steps of: Configuring at least one waveform according toa mathematical model having at least one waveform parameter, said atleast one waveform to be coupled to a target pathway structure; Choosinga value of said at least one waveform parameter so that said at leastwaveform is configured to be detectable in said target pathway structureabove background activity in said target pathway structure; Generatingan electromagnetic signal from said configured at least one waveform;and Coupling said electromagnetic signal to said target pathwaystructure using a coupling device. 2) The method of claim 1, whereinsaid target pathway structure includes at least one of a molecule, acell, a tissue, and an organ. 3) The method of claim 1, wherein said atleast one waveform parameter includes at least one of a frequencycomponent parameter that configures said at least one waveform to bebetween about 0.01 Hz and about 100 MHz, a burst amplitude envelopeparameter that follows an arbitrary amplitude function, a burstamplitude envelope parameter that follows a defined amplitude function,a burst width parameter that varies at each repetition according to anarbitrary width function, a burst width parameter that varies at eachrepetition according to a defined width function, a peak inducedelectric field parameter varying between about 1 μV/cm and: about 100mV/cm in said target pathway structure, and a peak induced magneticelectric field parameter varying between about 1 μT and about 0.1 T insaid target pathway structure. 4) The method of claim 3, wherein saiddefined amplitude function includes at least one of a 1/frequencyfunction, a logarithmic function, a chaotic function, and an exponentialfunction. 5) The method of claim 1, wherein said step of choosing avalue of at least one waveform parameter further includes the step ofchoosing a value of said at least one waveform parameter to satisfy aSignal to Noise Ratio model. 6) The-method of claim 1, wherein said stepof choosing a value of at least one waveform parameter further includesthe step of choosing a value of said at least one waveform parameter tosatisfy a Power Signal to Noise Ratio model. 7) The method of claim 1wherein said step of generating an electromagnetic signal furtherincludes the step of inductive generation of said electromagneticsignal. 8) The method of claim 1, wherein said step of generating anelectromagnetic signal further includes the step of capacitivegeneration of said electromagnetic signal. 9) The method of claim 1,wherein said step of coupling said electromagnetic signal furtherincludes the step of coupling said electromagnetic signalelectrochemically to said target pathway structure. 10) The method ofclaim 1, wherein said step of coupling said electromagnetic signalfurther includes the step of coupling said electromagnetic signalelectrostatically to said target pathway structure. 11) The method ofclaim 1, wherein said coupling device includes an inductor. 12) Themethod of claim 1, wherein said coupling device includes an electrode.13) The method of claim 1, further comprising the step of using at leastone of standard medical therapies and non-standard medical therapiesadjunctively with said electromagnetic treatment. 14) The method ofclaim 1, further comprising the step of using at least one of standardphysical therapies and non-standard physical therapies conjunctivelywith said electromagnetic treatment. 15) The method of claim 1, furthercomprising the step of using said electromagnetic treatment to modulatethe production and utilization of growth factors, cytokines, andregulatory substances by living cells. 16) The method of claim 1,further comprising the step of using said electromagnetic treatment tomodulate tissue growth and repair. 17) The method of claim 1, furthercomprising the step of using said electromagnetic treatment to reducechronic and acute pain of musculoskeletal and neural origin. 18) Themethod of claim 1, further comprising the step of using saidelectromagnetic treatment to reduce edema. 19) The method of claim 1,further comprising the step of using said electromagnetic treatment fortreatment of diabetic and pressure ulcers wherein said ulcers arechronic. 20) The method of claim 1, further comprising the step of usingsaid electromagnetic treatment for at least one of increasing blood flowand microvascular blood perfusion. 21) The method of claim 1, furthercomprising the step of using said electromagnetic treatment for at leastone of neovascularization and angiogenesis. 22) The method of claim 1,further comprising the step of using said electromagnetic treatment toenhance immune response for malignant and benign conditions. 23) Themethod of claim 1, further comprising the step of using saidelectromagnetic treatment to enhance transudation. 24) The method ofclaim 1, further comprising the step of using a positioning device todeliver said electromagnetic treatment to said plants, animals, andhumans. 25) The method of claim 24, wherein said positioning devicecomprises at least one of an anatomical support, an anatomical wrap, andapparel. 26) The method of claim 24, wherein said apparel includes atleast one of garments, fashion accessories, and footware. 27) The methodof claim 24, wherein said positioning Device is portable. 28) The methodof claim 24, wherein said positioning device is disposable. 28) Themethod of claim 24, wherein said positioning Device is implantable. 30)An electromagnetic treatment apparatus for plants, animals, and humanscomprising: A waveform configuration means for configuring at least onewaveform to be coupled to a target pathway structure according to amathematical model having at least one waveform parameter capable ofbeing chosen so that said at least one waveform is configured to bedetectable in said target structure above background activity in saidtarget pathway structure; An electromagnetic signal generating meansconnected to said waveform device by at least one connecting means forgenerating an electromagnetic signal from said configured at least onewaveform; and A coupling device connected by at least one connectingmeans to said electromagnetic signal generating device for coupling saidelectromagnetic signal to said target pathway structure. 31) Theelectromagnetic treatment apparatus of claim 30, wherein said targetpathway structure includes at least one of a molecule, a cell, a tissue,and an organ. 32) The electromagnetic treatment apparatus of claim 30,wherein said at least-one waveform parameter includes at least one of afrequency component parameter that configures said at least one waveformto be between about 0.01 Hz and about 100 MHz, a burst amplitudeenvelope parameter that follows an arbitrary amplitude function, a burstamplitude envelope parameter that follows a defined amplitude function,a burst width parameter that varies at each repetition according to anarbitrary width function, a burst width parameter that varies at eachrepetition according to a defined width function, a peak inducedelectric field parameter varying between about 1 μV/cm and about 100mV/cm in said target pathway structure, and a peak induced magneticelectric field parameter varying between about 1 μT and about 0.1 T insaid target pathway structure. 33) The electromagnetic treatmentapparatus of claim 30, wherein said defined amplitude function includesat least one of a 1/frequency function, a logarithmic function, achaotic function and an exponential function. 34) The electromagnetictreatment apparatus of claim 30, wherein a value of said at least onewaveform parameter is chosen to satisfy a Signal to Noise Ratio model.35) The electromagnetic treatment apparatus of claim 30, wherein a valueof at least one waveform parameter is chosen to satisfy a Power Signalto Noise Ratio model. 36) The electromagnetic treatment apparatus ofclaim 30, wherein said electromagnetic signal generating device includesan inductive generating device. 37) The electromagnetic treatmentapparatus of claim 30, lo wherein said electromagnetic signal generatingdevice includes a capacitive generating device. 38) The electromagnetictreatment apparatus of claim 30, wherein said coupling device includesan inductor. 39) The electromagnetic treatment apparatus of claim 30,wherein said coupling device includes an electrode. 40) Theelectromagnetic treatment apparatus of claim 30, further comprising apositioning device to position said electromagnetic treatment apparatusfor delivering treatment to said plants, animals and humans. 41) Theelectromagnetic treatment apparatus of claim 40, wherein saidpositioning device is at least one of an anatomical support, ananatomical wrap, and apparel. 42) The electromagnetic treatmentapparatus of claim 41, wherein said apparel includes at least one ofgarments, fashion accessories, and footware. 43) The electromagnetictreatment apparatus of claim 40, wherein said positioning device isportable. 44) The electromagnetic treatment apparatus of claim 40,wherein said positioning device is disposable. 45) The electromagnetictreatment apparatus of claim 40, wherein said positioning device isimplantable.